Substituted β diketones and their use

Abstract

The invention relates to the compounds of formula I:wherein one of X1 and X2 is MeSO2 and the other one is hydrogen or halogen and X3 is hydrogen or halogen. These compounds have been found to be useful in the prevention and the treatment of respiratory diseases, especially asthma, ARDS (Acute Respiratory Distress Syndrome), COPD (chronic obstructive pulmonary diseases), allergic rhinitis and related inflammatory conditions. More specifically, the invention relates to the use of said compound in the prevention and the treatment of asthma in steroid-resistant patients. The invention also relates to pharmaceutical formulations used in the treatment of said diseases.

What is claimed is:  
     
       1. Compounds of general formula I:                    
       wherein one of X 1  and X 2  is MeSO 2  and the other one is halogen and X 3  is hydrogen or halogen. 
     
     
       2. The compound of formula I wherein X 1  is halogen, X 2  is MeSO 2  and X 3  is hydrogen. 
     
     
       3. 3-{[3-Fluoro-4-(methylsulfonyl)-phenyl]methylene}-2,4-pentanedione. 
     
     
       4. 3-{[3-Chloro-4-(methylsulfonyl)-phenyl]methylene }-2,4-pentanedione. 
     
     
       5. 3-{[3-Bromo-4-(methylsulfonyl)-phenyl]methylene}-2,4-pentanedione. 
     
     
       6. 3-{[3,5-Dichloro-4-(methylsulfonyl)phenyl]methylene}-2,4-pentanedione. 
     
     
       7. 3-{[4-Chloro-3-(methylsulfonyl)phenyl]methylene}-2,4-pentanedione. 
     
     
       8. An inhalable pharmaceutical formulation containing a compound of formula I:                    
       wherein one of X 1  and X 2  is MeSO 2  and the other one is halogen and X 3  is hydrogen or halogen, having about 100% of its particle size below 10 μm, optionally in a suitable carrier or diluent. 
     
     
       9. The formulation according to claim  8 , wherein the carrier is lactose. 
     
     
       10. The formulation according to claim  8 , wherein it is a dry inhalation formulation. 
     
     
       11. A method for the prevention or treatment of inflammatory respiratory diseases wherein said method comprises administering to a mammal in need of said prevention or treatment an effective amount of the compound of general formula I′:                    
       wherein one of X 1  and X 2  is MeSO 2  and the other one is hydrogen or halogen and X 3  is hydrogen or halogen to prevent or treat said inflammatory respiratory diseases. 
     
     
       12. The method of claim  11 , wherein the compound is 3-[(4-methylsulfonylphenyl)methylene]-2,4-pentanedione. 
     
     
       13. The method of claim  11 , wherein the compound is 3-[(3-chloro-4-methylsulfonylphenyl)methylene]-2,4-pentanedione. 
     
     
       14. The method of claim  11 , wherein the disease is asthma. 
     
     
       15. The method of claim  11 , wherein the disease is steroid-resistant asthma. 
     
     
       16. The method of claim  11 , wherein the disease is Acute Respiratory Distress Syndrome. 
     
     
       17. The method of claim  11 , wherein the disease is chronic obstructive pulmonary disease.